Multiphoton Microscopy: A Potential “Optical Biopsy” Tool for Real-Time Evaluation of Lung Tumors Without the Need for Exogenous Contrast Agents

Jain, Manu; Narula, Navneet; Aggarwal, Amit; Stiles, Brendon M.; Shevchuk, Maria M.; Sterling, Joshua; Salamoon, Bekheit; Chandel, Vishal; Webb, Watt W.; Altorki, Nasser K.; Mukherjee, Sushmita

doi:10.5858/arpa.2013-0122-oa

Cited by 37 publications

(30 citation statements)

References 39 publications

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“…Like other multi-photon techniques [10][11][12][13][14][15][16][17][18], THG not only enables the recording of label-free images of unfixed 3D volumes of tissue [1][2][3][4][5][6][7][8][9][10] free from spatial distortion artifacts inherent to histopathology, but also potentially allows feedback on the nature of the tissue, i. e. whether it is healthy or tumorous, to the surgeon during surgery, as the relative speed of the imaging modalities approaches 'real' time, and no preparation steps of the tissue are required [5,6,[19][20][21][22][23]. THG was shown recently to yield label-free images of ex-vivo human tumor tissue of histopathological quality, in real-time [6].…”

Section: Introductionmentioning

confidence: 99%

Quantitative comparison of 3D third harmonic generation and fluorescence microscopy images

Zhang

Kuzmin

Groot

et al. 2017

Journal of Biophotonics

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Third harmonic generation (THG) microscopy is a label-free imaging technique that shows great potential for rapid pathology of brain tissue during brain tumor surgery. However, the interpretation of THG brain images should be quantitatively linked to images of more standard imaging techniques, which so far has been done qualitatively only. We establish here such a quantitative link between THG images of mouse brain tissue and all-nuclei-highlighted fluorescence images, acquired simultaneously from the same tissue area. For quantitative comparison of a substantial pair of images, we present here a segmentation workflow that is applicable for both THG and fluorescence images, with a precision of 91.3 % and 95.8 % achieved respectively. We find that the correspondence between the main features of the two imaging modalities amounts to 88.9 %, providing quantitative evidence of the interpretation of dark holes as brain cells. Moreover, 80 % bright objects in THG images overlap with nuclei highlighted in the fluorescence images, and they are 2 times smaller than the dark holes, showing that cells of different morphologies can be recognized in THG images. We expect that the described quantitative comparison is applicable to other types of brain tissue and with more specific staining experiments for cell type identification.

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Section: Introductionmentioning

confidence: 99%

Quantitative comparison of 3D third harmonic generation and fluorescence microscopy images

Zhang

Kuzmin

Groot

et al. 2017

Journal of Biophotonics

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“…The various components of the atherosclerotic plaques were defined based on their morphological features (similar to that seen on H&E) as well as their well-known autofluorescence or SHG signals on MPM (Denk et al, 1990;Zipfel et al, 2003;Tewari et al, 2011;Jain et al, 2014;Jain et al, 2015;Jain et al, 2016). All the H&E images shown in the figures correspond to the samples imaged with MPM.…”

Section: Resultsmentioning

confidence: 99%

A component‐by‐component characterisation of high‐risk atherosclerotic plaques by multiphoton microscopic imaging

Jain

Pisapia

et al. 2017

Journal of Microscopy

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Recognition of the distinct signatures of various plaque components suggests that MPM has the potential to offer next-generation characterisation of atherosclerotic plaques. The higher lateral resolution (comparable to histology) images generated by MPM for identifying plaque components might complement larger field of view and greater imaging depth currently available with optical coherence tomography imaging. As the next step MPM would need to be evaluated for intact vessel imaging ex vivo and in vivo.

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“…in the cell cytoplasm, was colour‐coded blue. Nuclei do not fluoresce with MPM but appear as signal‐void structures in a background of fluorescent cytoplasm . The signals from all three channels were collected and merged for better visual appreciation of the images.…”

Section: Methodsmentioning

confidence: 99%

“…Multiphoton microscopy (MPM) is a non‐linear imaging approach that can image fresh unprocessed tissue at cellular resolution without use of any exogenous dyes . Although the miniaturization of MPM probes for in vivo imaging is in progress , in the present study, we explore the ability of a commercial bench‐top MPM system in differentiating neoplastic from non‐neoplastic kidney tissue and characterizing various subtypes of kidney tumours in fresh ex vivo human nephrectomy specimens.…”

Section: Introductionmentioning

confidence: 99%

Multiphoton microscopy for rapid histopathological evaluation of kidney tumours

et al. 2015

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ObjectiveTo explore the potential of multiphoton microscopy (MPM) for rapid evaluation and triaging of ex vivo kidney tissue. Materials and MethodsFresh neoplastic and non-neoplastic tissues from nephrectomy specimens (n = 40) were imaged with MPM and later submitted for routine histopathology. ResultsOn MPM, normal kidney architecture was evident and clearly distinguishable from tumour. Forty malignant tumours (20 clear-cell renal cell carcinomas [RCCs], 10 papillary RCCs, five chromophobe RCCs and five papillary urothelial carcinomas [UCs], as diagnosed by haematoxylin and eosin staining) were imaged and subtyped as non-papillary and papillary, based on their architecture. Non-papillary tumours were further classified based on their unique cytoplasmic signatures. Clear-cell RCCs had a predominant population of cells with fat droplets in cytoplasm. Chromophobe RCCs had cells with non-fatty/homogeneous cytoplasm and distinct intra-cytoplasmic granules. Papillary RCCs had single-celllined papillae with often abundant histiocytes in their core, whereas PUC had multi-layered urothelium-lined papillae. The diagnostic accuracy of tumour subtyping by two independent uropathologists was 95%. ConclusionsWe showed that MPM can reliably differentiate neoplastic from non-neoplastic kidney tissue and subtype kidney tumours in fresh, unprocessed tissue, MPM might therefore be useful as a rapid real-time diagnostic tool for the evaluation of kidney biopsies, and surgical margins in partial nephrectomies, to improve overall patient management.

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Multiphoton Microscopy: A Potential “Optical Biopsy” Tool for Real-Time Evaluation of Lung Tumors Without the Need for Exogenous Contrast Agents

Cited by 37 publications

References 39 publications

Quantitative comparison of 3D third harmonic generation and fluorescence microscopy images

Quantitative comparison of 3D third harmonic generation and fluorescence microscopy images

A component‐by‐component characterisation of high‐risk atherosclerotic plaques by multiphoton microscopic imaging

Multiphoton microscopy for rapid histopathological evaluation of kidney tumours

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